Comparisons of Different Forms of Glucocorticoid on the Recovery of Reproductive Function in Patients With 21α-hydroxylase Deficiency (CGP21)

The purpose of this study is to conduct an open, randomized controlled clinical trial, evaluating the effects of different dosage forms of glucocorticoid on the Recovery of Reproductive Function in Patients With 21α-hydroxylase Deficiency.

Study Overview

• Status: Not yet recruiting
• Conditions: Congenital Adrenal Hyperplasia
• Intervention / Treatment: Drug: Hydrocortisone; Drug: Prednisone; Drug: Dexamethasone

Detailed Description

In the present study, about 120 patients who are more than 14 years old and diagnosed with 21-hydroxylase deficiency will be enrolled from Ruijin Hospital, Shanghai Jiao Tong University School of Medicine in China. Randomisation was computer generated and stratified by subtype and gender. After screening, eligible subjects will be randomly treated with equivalent dose of hydrocortisone, prednisone or dexamethasone for one year.

The treatment regimen was as follows. Firstly, at least one month washout period (withdrawal) was performed before treatment. The initial dose of hydrocortisone (20mg/tablet) was 15mg/m2/day to the maximum dose of 60mg, which was orally administered in three times, with the dose ratio of 2:1:3, and the administration time was 8:00-15:00-21:00. The initial dose of prednisone (5mg/tablet) was 3mg/m2/day to the maximum dose of 15mg. The dosage ratio was 1:2 and the administration time was 8:00 and 21:00. The initial dose of dexamethasone (0.75mg/tablet) was 0.3mg/m2/day to the maximum dose of 0.75mg and the administration time was 21:00.

The primary objective was to evaluate the effects of different dosage forms of glucocorticoid on the recovery of reproductive function in patients with 21α-hydroxylase deficiency. The primary end point is to evaluate menstrual cycles with ovulation in female patients (including menstrual period, menstrual frequency per year) and sperm count in male patients among the three groups. The secondary endpoint were: 1) The levels of progesterone, 17OHP, testosterone, androstenedione, sex hormone binding protein were measured at follicular phase in female patients and male unlimited in the first month and every three months thereafter; 2) The change of BMI, waist circumference, hip circumference, visceral and subcutaneous fat area, body and liver fat content after one year treatment; 3) The change of blood pressure, fasting blood glucose, fasting insulin, HbA1c, blood lipid profile after one year treatment; 4) The change of bone mineral density after one year; 5) The change of mental health status compared with baseline after one year follow-up.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Guang Ning, MD, PHD; Phone Number: 671817 +8621-64370045; Email: guangning@medmail.com.cn
• Study Contact Backup: Name: Shouyue Sun, Master of Medicine; Phone Number: 671817 +8621-64370045; Email: ssy10926@rjh.com.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Ruijin Hospital,Shanghai Jiao Tong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 41 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients diagnosed with 21α-OHD. The reference standard was baseline 17OHP (in the morning of follicular phase in female patients, men unlimited) or after cosyntropin stiimulation > 10ng/ml;
2. Age: >14 years old;
3. Post-puberty;

Exclusion Criteria:

1. Other diseases present with adrenocortical dysfunction, such as primary adrenal hypofunction, Cushing's syndrome, pituitary tumor, etc;
2. Other diseases with hyperandrogenemia were not treated, such as ovarian tumor;
3. Other diseases with HPG axis dysfunction were not treated, such as severe obesity (BMI > 35kg / m2), anorexia nervosa, thyroid dysfunction, etc;
4. Other diseases causing ovarian dysfunction, such as ovarian tumor, endometriosis, primary ovarian failure, etc;
5. History of adrenal and / or pituitary surgery;
6. Elevated AST/ALT (AST > 35 U/L, ALT > 55 U/L)
7. Other diseases need glucocorticoid treatment, such as autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis, autoimmune diseases such as wind dampness heat, rheumatic myocarditis, idiopathic pulmonary fibrosis, autoimmune liver disease, inflammatory bowel disease and amyloidosis, and allergic diseases such as bronchial asthma, exogenous allergic alveolitis and serum diseases, acute urticaria, vascular edema, hematological diseases such as idiopathic thrombocytopenic purpura, immune hemolysis and aplastic anemia, granulocytopenia, other iritis, keratitis, severe drug-induced dermatitis, eczema, etc.
8. Other diseases may lead to the failure of research intervention;
9. Are currently participating in another intervention study or participating in other drug clinical trials within 30 days;
10. No informed consent was signed;
11. According to the researcher's judgment, there is any situation affecting the study compliance;
12. Any other circumstances that are considered by the doctor to be prohibited from participating in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group hydrocortisone	Drug: Hydrocortisone; The initial dose of hydrocortisone (20mg/tablet) was 15mg/m2/day to the maximum dose of 60mg, which was orally administered in three times, with the dose ratio of 2:1:3, and the administration time was 8:00-15:00-21:00.
Experimental: Group Prednisone	Drug: Prednisone; The initial dose of prednisone (5mg/tablet) was 3mg/m2/day to the maximum dose of 15mg. The dosage ratio was 1:2 and the administration time was 8:00 and 21:00.
Experimental: Group Dexamethasone	Drug: Dexamethasone; The initial dose of dexamethasone (0.75mg/tablet) was 0.3mg/m2/day to the maximum dose of 0.75mg and the administration time was 21:00.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The number of ovulatory menstruation in female patients	up to 1 year
The average sperm count in male patients	up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The average levels of progesterone	Progesterone will be detected at follicular phase (day 2~8) in female patients.	up to 1 year
Mean serum concentrations of 17OHP		up to 1 year
Mean serum concentrations of testosterone		up to 1 year
Mean serum concentrations of androstenedione		up to 1 year
Change in BMI		up to 1 year
Change in waist circumference		up to 1 year
Change in blood pressure		up to 1 year
Change in fasting glucose levels		up to 1 year
Change in fasting insulin levels		up to 1 year
Change in 2-hour postprandial glucose levels		up to 1 year
Change in 2-hour postprandial insulin levels		up to 1 year
Change in bone mineral density		up to 1 year
Change in blood metabolomics profile measurement	In aid of LC/MS and GC-MS technique, we will measure the metabolomics molecular profile in blood samples before and after treatment. The metabolomics measurement will help to detect the profile of all kinds of hormones, bile acid species, lipids species and amino acid species.	up to 1 year
mental health status	The Self-reporting inventory ( SCL-90) will be used to evaluate the changes of patients' psychological state at baseline and after one-year treatment from 10 aspects, including somatization, obsessive-compulsive symptoms, interpersonal sensitivity, depression, anxiety, hostility, terror, paranoia, psychotic and others.	up to 1 year

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2020
• Primary Completion (Anticipated): September 30, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: August 23, 2020
• First Submitted That Met QC Criteria: August 28, 2020
• First Posted (Actual): September 2, 2020

Study Record Updates

• Last Update Posted (Actual): September 2, 2020
• Last Update Submitted That Met QC Criteria: August 28, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Endocrine System Diseases; Gonadal Disorders; Disorders of Sex Development; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Adrenal Gland Diseases; Steroid Metabolism, Inborn Errors; Hyperplasia; Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone; Prednisone; Hydrocortisone
• Other Study ID Numbers: CCEMD-20200819

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No